A simple catalytic system based on PdCl2(CH3CN) 2 in water for cross-coupling reactions using diazonium salts

Article abstract of DOI:10.1016/j.tet.2013.09.010

Aryl-heteroaryl and heteroaryl-heteroaryl compounds are obtained through the Suzuki-Miyaura cross-coupling reactions between diazonium salts and potassium trifluoroborates using PdCl₂(CH₃CN)₂ as the catalyst in water and in the absence of any additive, ligand or base. In addition, the same mild catalytic system is effective for the Matsuda-Heck reaction between several monoolefins with aryldiazonium salts.

Full text of DOI:10.1016/j.tet.2013.09.010

Tetrahedron xxx (2013) 1e5
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Tetrahedron
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A simple catalytic system based on PdCl2(CH3CN)2 in water
for cross-coupling reactions using diazonium salts
*
*
ꢀ
Ouissam El Bakouri, Martí Fernandez, Sandra Brun, Anna Pla-Quintana , Anna Roglans
ꢁ
Institut de Química Computacional i Catalisi (IQCC) and Departament de Química, Universitat de Girona, Campus de Montilivi, 17071 Girona, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 19 July 2013
Received in revised form 3 September 2013
Accepted 4 September 2013
Available online xxx
Aryleheteroaryl and heteroaryleheteroaryl compounds are obtained through the SuzukieMiyaura cross-
coupling reactions between diazonium salts and potassium trifluoroborates using PdCl2(CH3CN)2 as the
catalyst in water and in the absence of any additive, ligand or base. In addition, the same mild catalytic
system is effective for the MatsudaeHeck reaction between several monoolefins with aryldiazonium
salts.
Ó 2013 Published by Elsevier Ltd.
Keywords:
Palladium
Diazonium salts
Cross-coupling reactions
Aqueous medium
1. Introduction
Zarei's work:
Pd(OAc)2
ArN2OSO3-SiO2
+
NaBPh4
Ar
The palladium-catalyzed SuzukieMiyaura reaction is a widely
used method for the construction of CeC bonds.1 Among the
available range of electrophiles, aryldiazonium salts are a particu-
larly good choice since they allow Pd-catalyzed carbonecarbon
bond-forming reactions to be run under simple mild conditions.2
These salts are obtained from readily accessible anilines,3 which
are cheaper than the commonly used aryl halides and triflates, and
are highly reactive as electrophiles in the palladium-catalyzed
cross-coupling reactions at room temperature even in the ab-
sence of a base and added ligands. The potential of these processes
would be increased if they were run in an environmentally friendly
reaction media, such as water.
Na2CO3, H2O, r.t.
Cacchi's work:
alginate/gellan stabilized
Pd nanoparticles
Ar1N2BF4
Ar2BF3K
Ar1 Ar2
+
H2O, 40ºC
This work:
PdCl2(CH3CN)2
ArN2BF4
+
HetArBF3K
Ar HetAr
H2O, r.t. or 40ºC
PdCl2(CH3CN)2
HetArN2BF4 + Ar/HetArBF3K
HetAr
Ar/HetAr
H2O, r.t. or 40ºC
Despite the significant advances made in palladium-catalyzed
bond-forming reactions using chlorides or triflates in water,4 only
some recent reports have described the use of aryldiazonium salts
as electrophiles in SuzukieMiyaura reactions in water as the only
reaction solvent (Scheme 1). Zarei et al. prepared aryldiazonium
silica sulfates by supporting the diazonium salts on the surface of
silica sulfuric acid for use in Suzuki cross-couplings.5 These authors
described the SuzukieMiyaura cross-coupling of aryldiazonium
silica sulfates with sodium tetraphenylborate. In the presence of
Pd(OAc)2 and Na2CO3 in heterogeneous conditions, biaryls were
afforded in good yields in water media. The authors only used
Scheme 1. CeC bond-forming reactions with diazonium salts in water.
sodium tetraphenylborate as the boron counterpart limiting the
number of biphenyls obtained (Scheme 1). In addition, Cacchi et al.6
used palladium nanoparticles stabilized by an alginate/gellan
mixture as a recyclable catalytic system for SuzukieMiyaura
reactions of aryldiazonium tetrafluoroborates with potassium
aryltrifluoroborates in water (Scheme 1).
None of these previous studies applied the methodology to
heteroaromatic substrates in the diazonium electrophile or in the
boronic counterpart. This would be highly desirable in view of the
widespread appearance of heterocycles in biologically and phar-
maceutically active compounds as well as in advanced materials.
Hydrogen-bonding between water and heteroatoms has been
* Corresponding authors. Tel.: þ34 972 418275; fax: þ34 972 418150; e-mail
address: anna.roglans@udg.edu (A. Roglans).
0040-4020/$ e see front matter Ó 2013 Published by Elsevier Ltd.
http://dx.doi.org/10.1016/j.tet.2013.09.010
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2
O. El Bakouri et al. / Tetrahedron xxx (2013) 1e5
postulated as minimizing palladium deactivation by the co-
ordination of heterocycles.7
To evaluate the scope of the process, a variety of selected het-
eroaryltrifluoroborates were reacted with aryldiazonium salts with
electron-donating and electron-withdrawing groups (Table 2).
In previous studies in our group, aryl and heteroaryldiazonium
salts were shown to be effective partners in palladium-catalyzed
CeC bond-forming reactions in aqueous organic medium.8 In
view of the benefits of diazonium salts in palladium chemistry and
water as the reaction media for reactions involving heterocycles,
we envisioned a simple and effective reaction to involve hetero-
cycles in palladium-catalyzed CeC bond-forming reactions. Here
we present our results of the use of aryldiazonium salts in the
synthesis of heteroarylearyl and biheteroaryl derivatives by
SuzukieMiyaura cross-couplings in water (Scheme 1).
Table 2
SuzukieMiyaura cross-coupling reactions of aryldiazonium salts (1) and potassium
heteroaryltrifluoroborates 2, 4e6a
N2BF4
HetAr
PdCl2(CH3CN)2
H2O
+
HetAr-BF3K
2, 4-6
X
1a-1f
X
3, 7-19
2. Results and discussion
BF3K
O
S
BF3K
BF3K
S
We started the study by attempting the SuzukieMiyaura cross-
coupling to afford heteroarylearyl derivatives. It was decided to
test potassium organotrifluoroborates9 as boron counterparts since
they are less prone to protodeboronation and have been shown to
be highly effective in combination with aryldiazonium salts both by
our group8c,d and others.6,10 PdCl2, Pd(OAc)2, PdCl2(CH3CN)2, and
Pd(dba)2 were chosen from the range of simple, commercially
available catalysts. The model reaction chosen was between
4-acetylphenyldiazonium salt 1a and potassium benzofuran-2-
trifluoroborate 2 (Table 1).
BF3K
Br
S
2
4
6
5
Entry
1 (X)
HetAr-BF3K
Catalyst
(mol %)
Reaction
conditions
Product
(yield %)b,c
1d
2
3
4
5
1a (4-COMe)
1a (4-COMe)
1b (4-Me)
1c (4-NO2)
1f (2-Me)
1a (4-COMe)
1b (4-Me)
1d (4-OMe)
1d (4-OMe)
1a (4-COMe)
1a (4-COMe)
1b (4-Me)
1c (4-NO2)
1d (4-OMe)
1e (4-F)
2
2
2
2
2
4
4
4
4
5
5
5
5
5
5
6
6
6
10
5
5
5
5
5
5
10
5
10
5
5
5
5
5
5
10
5
25 ꢀC/3.5 h
40 ꢀC/4 h
40 ꢀC/4 h
40 ꢀC/4 h
40 ꢀC/4 h
40 ꢀC/4 h
40 ꢀC/4 h
25 ꢀC/1.5 h
40 ꢀC/4 h
25 ꢀC/1.5 h
40 ꢀC/4 h
40 ꢀC/4 h
40 ꢀC/4 h
40 ꢀC/4 h
40 ꢀC/4 h
40 ꢀC/4 h
25 ꢀC/6 h
40 ꢀC/4 h
3 (98)
3 (99)
7 (92)
8 (96)
9 (22)e
10 (27)
11 (61)
12 (57)
12 (53)
13 (63)
13 (58)
14 (45)
15 (53)
16 (35)
17 (49)
18 (31)e
19 (60)
19 (61)
6
7
8d
9
Table 1
10
11
12
13
14
15
16
17d
18
Screening of the reaction conditions for SuzukieMiyaura cross-couplinga
N2BF4
O
O
"Pd"
H2O
BF3K
+
COMe
MeOC
2
3
1a
1b (4-Me)
1c (4-NO2)
1c (4-NO2)
Entry
Catalyst (mol %)
Reaction conditions
Yield of 3b (%)
1
PdCl2 (10)
25 ꢀC/5 h
25 ꢀC/2 h
25 ꢀC/3.5 h
25 ꢀC/3 h
40 ꢀC/1.5 h
40 ꢀC/1.5 h
40 ꢀC/4 h
98
57c
98
2
Pd(OAc)2 (10)
a
Unless otherwise noted the reaction conditions used were: diazonium salt 1a
(0.15 mmol), potassium trifluoroborate 2 (0.18 mmol) in water (8 mL).
3
4
PdCl2(CH3CN)2 (10)
Pd(dba)2 (10)
82d
95
b
Isolated yields after column chromatography.
5
PdCl2(CH3CN)2 (10)
PdCl2(CH3CN)2 (5)
PdCl2(CH3CN)2 (1)
c
All crude reaction mixtures were analyzed by GCeMS and, unless otherwise
noted, showed only traces of potassium trifluoroborate homocoupling and/or
6e
7f
99
70
phenol.
d
a
Reaction run in 16 mL of water as a solvent and monitored until completion.
Phenol was detected by the GCeMS of the crude reaction mixture.
Unless otherwise noted the reaction conditions used were: diazonium salt 1a
(0.15 mmol), potassium trifluoroborate 2 (0.18 mmol) in water (16 mL).
e
b
Isolated yield after column chromatography.
12% yield of the aryldiazonium homocoupling product was obtained.
16% yield of the aryldiazonium homocoupling product was obtained.
Reaction run in 8 mL of water as a solvent.
c
d
Potassium benzofuran-2-trifluoroborate 2 proved to be efficient
in this type of process using several aryldiazonium salts with
electron-deficient (Table 2, entries 1, 2, 4) or electron-neutral (Table
2, entry 3) substituents. In all cases, reactions took place with ex-
cellent yields at 40 ꢀC in short reaction times. The reaction was
seriously affected by steric hindrance and only a 22% yield was
obtained when 2-methylphenyl diazonium tetrafluoroborate 1f
was used (Table 2, entry 5). Potassium trifluoroborates based on
sulfur heteroatoms, such as benzothiophene 4, and thiophene de-
rivatives 5 and 6 were then evaluated. Whereas a poor yield was
obtained when benzothiophene 4 was reacted with an electron-
deficient diazonium salt (Table 2, entry 6), better yields were ach-
ieved when electron-neutral (Table 2, entry 7) or electron-rich
(Table 2, entries 8 and 9) substituted diazonium salts were in-
volved in the reaction. In the case of the arylation of the 3-position
of thiophene (Table 2, entries 10e15), the efficacy of the process
was found to be independent from the electronic nature of the
aryldiazonium partner. It is notable that a bromide on the thio-
phene ring, such as in 6 remains intact during the course of the
reaction, although electron-deficient substituted diazonium salts
need to be used to achieve good yields of the coupling product
(compare in Table 2 the entries 16 and 17). Analogous results can be
e
f
Reaction run in 4 mL of water as a solvent.
When a 10% M of PdCl2 was used at room temperature a 98%
yield of the cross-coupled product 3 was obtained after 5 h of re-
action (Table 1, entry 1). Using Pd(OAc)2, the yield of 3 dropped to
57% and a 12% yield of homocoupling of the diazonium salt 1a was
also isolated (Table 1, entry 2). PdCl2(CH3CN)2 also gave excellent
results and in only 3.5 h of reaction (Table 1, entry 3). Using a pal-
ladium(0) source, such as Pd(dba)2, the yield of 3 was slightly lower
and a 16% yield of aryldiazonium homocoupled product was
obtained (Table 1, entry 4). In the following experiments,
PdCl2(CH3CN)2 was chosen as the best catalyst. Increasing the
temperature to 40 ꢀC resulted in a decrease in the reaction time to
afford an analogous yield (Table 1, entry 5). The reduction in the
catalyst loading was checked at this temperature. As we can see in
entry 6 of Table 1, the reaction also worked effectively when the
quantity of PdCl2(CH3CN)2 was reduced to 5%. However, using
a 1 mol % of palladium source, the yield was considerably lower and
the reaction time increased (Table 1, entry 7).
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O. El Bakouri et al. / Tetrahedron xxx (2013) 1e5
3
obtained with a 10 mol % of catalyst at room temperature and with
5 mol % loading with gentle heating (compare in Table 2, the entries
1 and 2, 8 and 9, and 17 and 18).
water and being aware that Correia et al. recently described the
use of this complex as a catalyst in the enantioselective Heck
coupling in methanol,17 we decided to investigate whether it was
also effective as a catalyst in the MatsudaeHeck reaction in water.
The results are shown in Table 4.
The SuzukieMiyaura cross-coupling when the heteroaromatic
framework is in the diazonium electrophile was then studied. The
thiophene diazonium salt 20 was successfully coupled with several
aryltrifluoroborates 21aec and potassium benzofurantrifluoroborate
2 using 10 mol % of PdCl2(CH3CN)2 at room temperature (Table 3). In
the case of potassium 4-fluorophenytrifluoroborate 21c, gentle
heating to 40 ꢀC was needed to achieve a good yield of the cross-
coupled product. Finally, the reaction between two heteroaromatic
partners was evaluated (Table 3, entry 5). A 65% yield was achieved
in 4.5 h for the coupling reaction in water at room temperature.
Table 4
MatsudaeHeck reactions of aryldiazonium salts (1) and olefins 26a
N2BF4
R
R
5 mol% PdCl2(CH3CN)2
+
H2O, 25 ºC
X
27-34
1b-f
26a-c
X
Entry
1 (X)
26 (R)
Reaction
time (h)
Product
Table 3
(yield %)b
Cross-coupling reactions of heteroaryldiazonium salt 20a
1
2
3
4
5
6
7
8
1b (4-Me)
1c (4-NO2)
1d (4-OMe)
1e (4-F)
1f (2-Me)
1b (4-Me)
1e (4-F)
26a (COOtBu)
26a (COOtBu)
26a (COOtBu)
26a (COOtBu)
26a (COOtBu)
26b (Ph)
8
1.5
5
1.5
7
3
27 (89)
28 (96)
29 (81)
30 (99)
31 (69)
32 (55)
33 (28)
34 (66)
BF3K
Y
Y
21a-c
10 mol% PdCl2(CH3CN)2
26b (Ph)
26c (PO(OEt)2)
7
2
CO2Me
22-24
S
H2O
1d (4-OMe)
N2BF4
a
The reaction conditions used were: diazonium salt 1 (0.18 mmol), alkene 26
(0.30 mmol) in water (8 mL).
CO2Me
S
b
O
Isolated yields after column chromatography.
BF3K
20
2
O
10 mol% PdCl2(CH3CN)2
H2O
tert-Butyl acrylate 26a was arylated in excellent yields with
aryldiazonium salts containing both electron-donating and
electron-withdrawing substituents (Table 4, entries 1e4). ortho
Substituents were tolerated and diazonium salt 1f bearing an ortho
methyl substituent reacted to give a 69% yield of the arylated
product (Table 4, entry 5). Styrene was a poor substrate in this re-
action giving only moderate yields of the stilbene derivatives,
probably due to the low miscibility of styrene with water (Table 4,
entries 6 and 7). Diethyl vinylphosphonate 26c was also active in
the MatsudaeHeck reaction giving a 66% yield of compound 34
(Table 4, entry 8). The arylation of olefins 26aec only gave products
with the (E)-configuration, as was confirmed by the large coupling
constant values (16e18 Hz) observed between the olefin protons
for all compounds 27e34. No residual proton signals from tentative
(Z)-configuration isomers were observed.
CO2Me
S
25
Entry
Reagent
Reaction conditions
Product (yield %)b
1
2
3
4
5
21a (Y¼3-F)
21b (Y¼H)
21c (Y¼4-F)
21c (Y¼4-F)
2
25 ꢀC/1 h
25 ꢀC/1 h
25 ꢀC/2 h
40 ꢀC/1 h
25 ꢀC/4.5 h
22 (45)
23 (56)
24 (26)
24 (50)
25 (65)c
a
The reaction conditions used were: diazonium salt 1a (0.15 mmol), potassium
trifluoroborate 2 (0.18 mmol) in water (16 mL).
b
Isolated yields after column chromatography.
23% yield of the potassium benzofuran-2-trifluoroborate homocoupling product
c
was obtained.
The MatsudaeHeck reaction with the heteroaromatic di-
azonium salt 20 was also tested. A moderate 33% yield was ach-
ieved by reacting 20 with tert-butyl acrylate using a 5 mol % catalyst
at 25 ꢀC. The yield could be improved to a 74% when increasing both
the catalyst loading and the temperature (Scheme 2).
The MatsudaeHeck reaction was first described by Sengupta
and Bhattacharya who used diazonium salts in water in an in situ
diazotization followed by Heck coupling with ethyl acrylate.11 The
use of water in this reaction has been studied in more detail in the
last couple of years. Two papers described the use of palladium
nanoparticles as catalysts. Gholinejad used palladium nano-
particles supported on agarose and prepared from Pd(OAc)2 for
the coupling of styrene and ethyl acrylate with four aryldiazonium
salts,12 and Pore and Gaikwad described the use of in situ formed
Pd nanoparticles from Pd(OAc)2 although with the addition of
a surfactant.13 Two other papers described the reaction by using
Pd(OAc)2. Zarei et al. used aryldiazonium silica sulfates for the
arylation of methyl acrylate, styrene, and acrylic acid to afford the
corresponding disubstituted olefins in good yields.14 More re-
COOtBu
COOtBu
N2BF4
26a
H2O / 4h
CO2Me
CO2Me
S
S
35
20
Conditions A: 5 mol% PdCl2(CH3CN)2 / 25 ºC; 33% yield
Conditions B: 10 mol% PdCl2(CH3CN)2 / 40 ºC; 74% yield
ꢀ
ꢀ
cently, Sebastian, Vallribera, Najera et al. applied the methodology
to the coupling of the readily available aryldiazonium tetra-
fluoroborates with a series of monosubstituted olefins.15 Finally,
Correia and Schwalm described the HeckeMatsuda arylation un-
der Pd(OAc)2 catalysis of an N-protected 3-pyrroline with aryl-
diazonium salt in water as the key step in the concise total
synthesis of marinoquinoline derivatives.16 All the precedents in
the literature used Pd(OAc)2 as the pre-catalyst. Having found that
PdCl2(CH3CN)2 effectively catalyzed SuzukieMiyaura reactions in
Scheme 2. MatsudaeHeck reaction with heteroaryldiazonium salt 20.
3. Conclusions
In summary, we have developed an experimentally simple
method for the cross-coupling of aryl and heteroaryldiazonium
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4
O. El Bakouri et al. / Tetrahedron xxx (2013) 1e5
salts with potassium aryl and heteroaryltrifluoroborates using
commercially available PdCl2(CH3CN)2, water as the only solvent,
and running the reactions under mild conditions (room tempera-
ture or 40 ꢀC) for short reaction times. The protocol is simple,
without the need for a base or ligands, and a wide range of func-
tional groups and heteroaromatic moieties are tolerated. In addi-
tion, the catalytic system described has also been tested in
MatsudaeHeck reactions in water following an experimentally
simple procedure.
7.25e7.35 (m, 5H), 7.54 (m, 1H), 7.63 (m, 1H), 7.88 (m, 1H); m/z (%)
(EI) 208 (100, Mþ).
4.2.5. 2-(4-Acetylphenyl)benzo[b]thiophene (10). Colorless solid;
mp¼183e184 ꢀC (lit. 165.2e166.7 ꢀC).22 dH (400 MHz, CDCl3, 25 ꢀC)
4
2.63 (s, 3H), 7.34e7.39 (m, 2H), 7.66 (d, JH,H¼0.8 Hz, 1H), 7.80 (d,
3JH,H¼8.8 Hz, 2H), 7.80e7.87 (m, 2H), 8.00 (d, 3JH,H¼8.8 Hz, 2H); m/z
(%) (EI) 252 (82, Mþ), 237 (100), 208 (47).
4.2.6. 2-(4-Methylphenyl)benzo[b]thiophene (11). Colorless solid;
mp¼153e155 ꢀC (lit.23 156.9e158.2 ꢀC); dH (300 MHz, CDCl3, 25 ꢀC)
2.38 (s, 3H), 7.20e7.24 (m, 2H), 7.16e7.36 (m, 2H), 7.48
4. Experimental section
4.1. General
4
3
(d, JH,H¼0.6 Hz, 1H), 7.60 (d, JH,H¼8.1 Hz, 2H), 7.74 (m, 1H), 7.80
(m, 1H); m/z (EI) 224 (100, Mþ).
Reaction mixtures were chromatographed through a silica gel
column (230e400 mesh). 1H NMR spectra were measured at
400 MHz and 300 MHz with Bruker instruments. 1H chemical shifts
4.2.7. 2-(4-Methoxyphenyl)benzo[b]thiophene (12).23 Colorless oil;
3
dH (300 MHz, CDCl3, 25 ꢀC) 3.85 (s, 3H), 6.96 (d, JH,H¼8.7 Hz, 2H),
3
(d) were referenced to internal solvent resonances and reported
7.25e7.40 (m, 2H), 7.42 (s, 1H), 7.64 (d, JH,H¼8.7 Hz, 2H), 7.75
(m, 1H), 7.80 (m, 1H); m/z (%) (EI) 240 (100, Mþ), 225 (56).
relative to SiMe4. GCeMS analyses were performed by an Agilent
7890A gas equipped with an HP-5 capillary column interfaced with
an Agilent 5975C mass spectrometer. The electron ionization (EI)
source was set at 70 eV.
Commercially available potassium organotrifluoroborates 2,
4e6, and 21aec, anilines, and olefins 26aec were used without
purification. Aryldiazonium salts 1aef and 20 were prepared by
treatment of the corresponding aniline with sodium nitrite and
HBF4 in aqueous media following the general method.3 These salts
can be stored for several months at ꢁ20 ꢀC.
4.2.8. 3-(4-Acetylphenyl)thiophene
(13).24 Colorless
solid;
mp¼149e151 ꢀC; dH (400 MHz, CDCl3, 25 ꢀC) 2.62 (s, 3H), 7.40e7.45
3
4
(m, 2H), 7.57 (dd, JH,H¼2.8 Hz, JH,H¼1.6 Hz, 1H), 7.68 (d,
3
3JH,H¼8.4 Hz, 2H), 7.99 (d, JH,H¼8.4 Hz, 2H); m/z (%) (EI) 202 (60,
Mþ), 187 (100), 115 (65).
4.2.9. 3-(4-Methylphenyl)thiophene (14).24 Pale yellow solid;
mp¼97e99 ꢀC; dH (300 MHz, CDCl3, 25 ꢀC) 2.36 (s, 3H), 7.19
(d, 3JH,H¼8.0 Hz, 2H), 7.32e7.40 (m, 3H), 7.47 (d, 3JH,H¼8.0 Hz, 2H);
m/z (%) (EI) 174 (100, Mþ).
4.2. General procedure for the SuzukieMiyaura reactions
4.2.10. 3-(4-Nitrophenyl)thiophene
(15).25 Yellow
solid;
Potassium heteroaryltrifluoroborate (0.18 mmol) was added to
a solution of aryldiazonium tetrafluoroborate (0.15 mmol) and
PdCl2(CH3CN)2 (5 mol %, 1.9 mg) in H2O (8 mL) at 0 ꢀC. The resulting
mixture was warmed to room temperature (or heated to 45 ꢀC) and
was stirred until the reaction was completed (as observed by the
ceasing of the release of N2) (Tables 1e3). The reaction mixture was
extracted with CH2Cl2 (3ꢂ10 mL), the organic phase was then dried
and evaporated, and the crude material was purified by column
chromatography on silica gel (hexane/ethyl acetate, gradient) to
give the desired compound.
mp¼129e130 ꢀC; dH (400 MHz, CDCl3, 25 ꢀC) 7.43e7.48 (m, 2H),
3
3
7.63 (m, 1H), 7.74 (d, JH,H¼8.8 Hz, 2H), 8.25 (d, JH,H¼8.8 Hz, 2H);
m/z (%) (EI) 205 (98, Mþ), 115 (100).
4.2.11. 3-(4-Methoxyphenyl)thiophene
(16).26 Colorless
solid;
mp¼124e126 ꢀC; dH (400 MHz, CDCl3, 25 ꢀC) 3.83 (s, 3H), 6.93
(d, 3JH,H¼8.8 Hz, 2H), 7.30e7.38 (m, 3H), 7.52 (d, 3JH,H¼8.8 Hz, 2H);
m/z (%) (EI) 190 (100, Mþ), 147 (50).
4.2.12. 3-(4-Fluorophenyl)thiophene (17).26 Pale yellow oil; dH
3
(300 MHz, CDCl3, 25 ꢀC) 7.07 (t, JH,H¼3JH,F¼8.8 Hz, 2H), 7.30e7.39
4.2.1. 2-(4-Acetylphenyl)benzo[b]furan
(3). Colorless
solid;
3
4
mp¼170e172 ꢀC (lit.18 177e179 ꢀC); dH (300 MHz, CDCl3, 25 ꢀC) 2.61
(m, 3H), 7.54 (dd, JH,H¼8.8 Hz, JH,F¼5.2 Hz, 2H); m/z (%) (EI) 178
(100, Mþ).
4
3
(s, 3H), 7.13 (d, JH,H¼0.8 Hz, 1H), 7.25 (ddd, JH,H¼8.0 Hz,
3JH,H¼6.8 Hz, 4JH,H¼1.2 Hz,1H), 7.32 (ddd, 3JH,H¼8.0 Hz, 3JH,H¼6.8 Hz,
4JH,H¼1.2 Hz, 1H), 7.53 (dd, 3JH,H¼8.0 Hz, 4JH,H¼0.8 Hz, 1H), 7.59 (m,
4.2.13. 2-Bromo-5-(4-methylphenyl)thiophene (18).27 Pale yellow
wax; dH (300 MHz, CDCl3, 25 ꢀC) 2.35 (s, 3H), 6.99 (br s, 2H),
3
3
1H), 7.91 (d, JH,H¼8.8 Hz, 2H), 8.00 (d, JH,H¼8.8 Hz, 2H); m/z (EI)
236 (6, Mþ), 221 ð10; M ꢁ CH3þÞ; 44 (100%).
3
7.15e7.19 (m, 2H), 7.40 (d, JH,H¼8.1 Hz, 2H); m/z (%) (EI) 252e254
(100, Mþ), 129 (77).
4.2.2. 2-(4-Methylphenyl)benzo[b]furan
(7). Colorless
solid;
mp¼121e123 ꢀC (lit.19 124e125 ꢀC); dH (300 MHz, CDCl3, 25 ꢀC)
4.2.14. 2-Bromo-5-(4-nitrophenyl)thiophene (19). Yellow solid;
mp¼134e135 ꢀC (lit.28 124e125 ꢀC); dH (300 MHz, CDCl3, 25 ꢀC)
4
2.39 (s, 3H), 6.96 (d, JH,H¼0.9 Hz, 1H), 7.16e7.29 (m, 4H), 7.51 (m,
3
3
3
7.13 (d, JH,H¼3.0 Hz, 1H), 7.24 (d, JH,H¼3.0 Hz, 1H), 7.66 (d,
1H), 7.56 (m, 1H), 7.76 (d, JH,H¼8.1 Hz, 2H); m/z (%) (EI) 209 (22,
3JH,H¼9.0 Hz, 2H), 8.26 (d, JH,H¼9.0 Hz, 2H); m/z (%) (EI) 283e285
3
MþHþ), 55 (100).
(50, Mþ), 158 (100).
4.2.3. 2-(4-Nitrophenyl)benzo[b]furan
(8). Yellow
solid;
mp¼181e183 ꢀC (lit.20 184.5e185 ꢀC); dH (400 MHz, CDCl3, 25 ꢀC)
4.2.15. Methyl 3-(3-fluorophenyl)thiophene-2-carboxylate (22),
methyl 3-phenylthiophene-2-carboxylate (23), and methyl 3-(4-
fluorophenyl)thiophene-2-carboxylate (24). Compounds (22)e(24)
were previously described by us.8d
4
3
7.24 (d, JH,H¼0.8 Hz, 1H), 7.28 (m, 1H), 7.37 (ddd, JH,H¼8.4 Hz,
3JH,H¼7.2 Hz, 4JH,H¼1.2 Hz 1H), 7.56 (dd, 3JH,H¼8.0 Hz, 4JH,H¼0.8 Hz,
3
3
1H), 7.64 (m, 1H), 8.00 (d, JH,H¼8.8 Hz, 2H), 8.30 (d, JH,H¼8.8 Hz,
2H); m/z (%) (EI) 239 (6, Mþ), 44 (100).
4.2.16. Methyl 3-(2-benzo[b]furan)-thiophene-2-carboxylate
(25). Pale yellow solid; mp¼71e73 ꢀC; dH (300 MHz, CDCl3,
25 ꢀC) 3.95 (s, 3H), 7.25 (m, 1H), 7.33 (m, 1H), 7.50 (m, 1H),
4.2.4. 2-(2-Methylphenyl)benzo[b]furan (9).21 Yellow solid; dH
4
(300 MHz, CDCl3, 25 ꢀC) 2.61 (s, 3H), 6.92 (d, JH,H¼1.2 Hz, 1H),
Please cite this article in press as: El Bakouri, O.; et al., Tetrahedron (2013), http://dx.doi.org/10.1016/j.tet.2013.09.010

O. El Bakouri et al. / Tetrahedron xxx (2013) 1e5
5
3
3
7.53 (d, JH,H¼5.4 Hz, 1H), 7.65 (m, 1H), 7.73 (d, JH,H¼5.4 Hz,
(d, 3JH,H¼8.8 Hz, 2H), 7.46 (dd, 3JH,P¼22.8 Hz, 3JH,H¼17.6 Hz, 1H); m/z
1H), 7.94 (d, JH,H¼0.9 Hz, 1H); m/z (%) (EI) 258 (100, Mþ),
(%) (EI) 270 (8, Mþ), 161 (25), 44 (100).
4
227 (56).
4.3.9. Methyl 3[(E)-2-(tert-butoxycarbonyl)vinyl]thiophene-2-car-
boxylate (35). Compound (35) was previously described by us.8d
4.3. General procedure for the MatsudaeHeck reactions
Acknowledgements
Olefin (0.30 mmol) was added to a solution of aryldiazonium
tetrafluoroborate (0.18 mmol) and PdCl2(CH3CN)2 (5 mol %,
2.3 mg) in H2O (8 mL) at 0 ꢀC. The resulting mixture was warmed
to room temperature and stirred until the reaction was completed
(as observed by the ceasing of the release of N2) (Table 4 and
Scheme 2). The reaction mixture was extracted with CH2Cl2
(3ꢂ10 mL), the organic phase was then dried and evaporated and
the crude material was purified by column chromatography on
silica gel (hexane/ethyl acetate, gradient) to give the desired
compound.
Financial support from MICINN (CTQ2011-23121) of Spain and
‘Generalitat de Catalunya’ (2009SGR637) is acknowledged. S.B.
thanks the University of Girona for a predoctoral grant.
References and notes
1. For monographies, see: (a) Negishi, E. Handbook of Organopalladium Chemistry for
OrganicSynthesis;Wiley-Interscience:NewYork,NY;(b)deMeijere,A.;Diederich, F.
Metal-catalyzed Cross-coupling Reactions; Wiley-VCH: Weinheim, Germany.
~
2. For reviews, see: (a) Roglans, A.; Pla-Quintana, A.; Moreno-Manas, M. Chem.
Rev. 2006, 106, 4622e4643; (b) Felpin, F.-X.; Nassar-Hardy, L.; Le Callonnec, F.;
Fouquet, E. Tetrahedron 2011, 67, 2815e2831; (c) Taylor, J. G.; Moro, A. V.;
Correia, C. R. D. Eur. J. Org. Chem. 2011, 1403e1428.
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Chem. 1979, 44, 1572e1574.
4.3.1. tert-Butyl (E)-4-methylcinnamate (27).29 Pale yellow oil; dH
(400 MHz, CDCl3, 25 ꢀC) 1.53 (s, 9H), 2.36 (s, 3H), 6.31 (d,
3
3
3JH,H¼16.0 Hz, 1H), 7.16 (d, JH,H¼8.0 Hz, 2H), 7.39 (d, JH,H¼8.0 Hz,
4. For a recent review about cross-couplings using water as solvent, see: Alonso,
ꢀ
2H), 7.55 (d, JH,H¼16.0 Hz, 1H); m/z (%) (EI) 218 (8, Mþ), 162 (67,
3
D. A.; Najera, C. In Science of Synthesis. Water in Organic Synthesis; Kobayashi, S.,
Ed.; George Thieme: Stuttgart, 2012; Vol. 2011/7, pp 535e578.
5. Zarei, A.; Khazdooz, L.; Hajipour, A. R.; Rafiee, F.; Azizi, G.; Abrishami, F. Tet-
rahedron Lett. 2012, 53, 406e408.
t
[Mꢁ Bu]þ), 32 (100).
6. Cacchi, S.; Caponetti, E.; Casadei, M. A.; Giulio, A. D.; Fabrizi, G.; Forte, G.;
Goggiamani, A.; Moreno, S.; Paolicelli, P.; Petrucci, F.; Prastaro, A.; Saladino, M.
L. Green Chem. 2012, 14, 317e320.
4.3.2. tert-Butyl (E)-4-nitrocinnamate (28). Pale yellow solid;
mp¼148e150 ꢀC (lit.29 155e157 ꢀC); dH (400 MHz, CDCl3, 25 ꢀC)
1.55 (s, 9H), 6.49 (d, 3JH,H¼16.2 Hz, 1H), 7.61 (d, 3JH,H¼16.2 Hz, 1H),
7.65 (d, 3JH,H¼8.8 Hz, 2H), 8.23 (d, 3JH,H¼8.8 Hz, 2H); m/z (%) (EI) 234
(5, [MꢁMe]þ), 194 (28), 176 (30), 32 (100).
7. Fleckenstein, C. A.; Plenio, H. Chem. Soc. Rev. 2010, 39, 694e711.
~
8. (a) Masllorens, J.; Moreno-Manas, M.; Pla-Quintana, A.; Roglans, A. Org. Lett. 2003,
ꢀ
5, 1559e1561; (b) Masllorens, J.; Bouquillon, S.; Roglans, A.; Henin, F.; Muzart, J. J.
ꢀ
Organomet. Chem. 2005, 690, 3822e3826; (c) Masllorens, J.; Gonzalez, I.; Roglans,
ꢀ
A. Eur. J. Org. Chem. 2007, 158e166; (d) Raduan, M.; Padrosa, J.; Pla-Quintana, A.;
Parella, T.; Roglans, A. Adv. Synth. Catal. 2011, 353, 2003e2012.
4.3.3. tert-Butyl (E)-4-methoxycinnamate (29). Pale yellow oil (lit.30
34e35 ꢀC); dH (400 MHz, CDCl3, 25 ꢀC) 1.53 (s, 9H), 3.84 (s, 3H), 6.24
9. (a) Molander, G. A.; Ellis, N. Acc. Chem. Res. 2007, 40, 275e286; (b) Darses, S.;
^
Genet, J.-P. Chem. Rev. 2008, 108, 288e305; (c) Molander, G. A.; Canturk, B.;
3
3
Kennedy, L. E. J. Org. Chem. 2009, 74, 973e980.
(d, JH,H¼15.9 Hz, 1H), 6.89 (d, JH,H¼8.7 Hz, 2H), 7.46 (d,
^
10. Selected references: (a) Darses, S.; Jeffery, T.; Brayer, J. L.; Demoute, J. P.; Genet, J. P.
3
3JH,H¼8.7 Hz, 2H), 7.54 (d, JH,H¼15.9 Hz, 1H); m/z (%) (EI) 234 (10,
^
Bull. Soc. Chim. Fr. 1996, 133, 1095e1102; (b) Darses, S.; Genet, J. P.; Brayer, J. L.; De-
t
Mþ), 178 (64, [Mꢁ Bu]þ), 32 (100).
^
moute, J. P. Tetrahedron Lett.1997, 38, 4393e4396; (c) Darses, S.; Michaud, G.;Genet,
J.P. TetrahedronLett.1998, 39, 5045e5048;(d)Darses, S.;Michaud,G.;Genet, J. P.Eur.
^
J. Org. Chem. 1999, 1875e1883; (e) Frohn, H.-J.; Adonin, N. Y.; Bardin, V. V.; Star-
ichenko, V. F. J. Fluorine Chem. 2002,117,115e120; (f) Gallo, V.; Mastrorilli, P.; Nobile,
C. F.; Paolillo, R.; Taccardi, N. Eur. J. Inorg. Chem. 2005, 582e588; (g) Varnedoe, L. S.;
Angel, B. D.; McClellan, J. L.; Hanna, J. M., Jr. Lett. Org. Chem. 2010, 7,1e6; (h) Schmidt,
4.3.4. tert-Butyl (E)-4-fluorocinnamate (30). Colorless solid;
mp¼47.5e48.5 ꢀC (lit.29 44e46 ꢀC); dH (400 MHz, CDCl3, 25 ꢀC) 1.53
(s, 9H), 6.29 (d, 3JH,H¼16.0 Hz, 1H), 7.02e7.09 (m, 2H), 7.46e7.51 (m,
€
B.; Holter, F. Org. Biomol. Chem. 2011, 9, 4914e4920; (i) Peters, M.; Trobe, M.; Tan, H.;
3
2H), 7.54 (d, JH,H¼16.0 Hz, 1H); m/z (%) (EI) 222 (2, Mþ), 166 (12,
Kleineweischede, R.; Breinbauer, R. Chem.dEur. J. 2013, 19, 2442e2449.
11. Sengupta, S.; Bhattacharya, S. J. Chem. Soc., Perkin Trans. 1 1993, 1943e1944.
12. Gholinejad, M. Appl. Organomet. Chem. 2013, 27, 19e22.
13. Gaikwad, D. S.; Pore, D. M. Synlett 2012, 2631e2634.
t
[Mꢁ Bu]þ), 32 (100).
4.3.5. tert-Butyl (E)-2-methylcinnamate (31).31 Pale yellow oil; dH
(300 MHz, CDCl3, 25 ꢀC) 1.54 (s, 9H), 2.42 (s, 3H), 6.29 (d,
3JH,H¼15.7 Hz, 1H), 7.15e7.28 (m, 3H), 7.53 (m, 1H), 7.89 (d,
3JH,H¼15.7 Hz, 1H); m/z (%) (EI) 218 (10, Mþ), 32 (100).
14. Zarei, A.; Khazdooz, L.; Pirisedigh, A.; Hajipour, A. R.; Seyedjamali, H.; Aghaei, H.
Tetrahedron Lett. 2011, 52, 4554e4557.
ꢀ
ꢀ
15. Salabert, J.; Sebastian, R. M.; Vallribera, A.; Cívicos, J. F.; Najera, C. Tetrahedron
2013, 69, 2655e2659.
16. Schwalm, C. S.; Correia, C. R. D. Tetrahedron Lett. 2012, 53, 4836e4840.
17. Correia, C. R. D.; Oliveira, C. C.; Salles, A. G., Jr.; Santos, E. A. F. Tetrahedron Lett.
2012, 53, 3325e3328.
18. Kitamura, Y.; Sako, S.; Udzu, T.; Tsutsui, A.; Maegawa, T.; Monguchi, Y.; Sajiki, H.
Chem. Commun. 2007, 5069e5071.
19. Jaseer, E. A.; Prasad, D. J. C.; Sekar, G. Tetrahedron 2010, 66, 2077e2082.
20. Takeda, N.; Miyata, O.; Naito, T. Eur. J. Org. Chem. 2007, 1491e1509.
21. Kondolff, I.; Doucet, H.; Santelli, M. J. Heterocycl. Chem. 2008, 45, 109e118.
22. Sun, L.-L.; Deng, C.-L.; Tang, R.-Y.; Zhang, X.-G. J. Org. Chem. 2011, 76, 7546e7550.
23. Tamba, S.; Okubo, Y.; Tanaka, S.; Monguchi, D.; Mori, A. J. Org. Chem. 2010, 75,
6998e7001.
4.3.6. (E)-4-Methylstilbene (32). Colorless solid; mp¼117e119 ꢀC
(lit.32 118.5e119 ꢀC); dH (300 MHz, CDCl3, 25 ꢀC) 2.35 (s, 3H), 7.03 (d,
3JH,H¼16.6 Hz, 1H), 7.09 (d, 3JH,H¼16.6 Hz, 1H), 7.16 (d, 3JH,H¼8.1 Hz,
2H), 7.23 (tt, 3JH,H¼7.3 Hz, 4JH,H¼1.2 Hz, 1H), 7.30e7.37 (m, 2H), 7.40
(d, 3JH,H¼8.1 Hz, 2H), 7.47e7.51 (m, 2H); m/z (%) (EI) 195 (11, MþHþ),
55 (100).
24. Wu, X.; Rieke, R. D. J. Org. Chem. 1995, 60, 6658e6659.
25. Rieke, R. D.; Kim, S.-H.; Wu, X. J. Org. Chem. 1997, 62, 6921e6927.
26. Feuerstein, M.; Doucet, H.; Santelli, M. J. Organomet. Chem. 2003, 687, 327e336.
27. Mohapatra, S.; Holmes, B. T.; Newman, C. R.; Prendergast, C. F.; Frisbie, C. D.;
Ward, M. D. Adv. Funct. Mater. 2004, 14, 605e609.
28. Latassa, D.; Prim, D.; Kirsch, G. Heterocycl. Commun. 1998, 4, 81e94.
29. Gillespie, K. M.; Sanders, C. J.; O’Shaughnessy, P.; Westmoreland, I.; Thickitt, C.
P.; Scott, P. J. Org. Chem. 2002, 67, 3450e3458.
4.3.7. (E)-4-Fluorostilbene (33).33 Colorless solid; mp¼123e125 ꢀC;
3
dH (300 MHz, CDCl3, 25 ꢀC) 7.00 (d, JH,H¼16.6 Hz, 1H), 7.07 (d,
3JH,H¼16.6 Hz, 1H), 7.01e7.71 (m, 2H), 7.25 (m, 1H), 7.32e7.38 (m,
2H), 7.44e7.51 (m, 4H); m/z (%) (EI) 198 (100, Mþ), 183 (65), 177
(45), 98 (55).
30. Imashiro, R.; Seki, M. J. Org. Chem. 2004, 69, 4216e4226.
31. De Vries, A. H. M.; De Vries, J. G.; DSM N. V., Neth. PCT Int. Appl. NL 1017138, 2001.
32. Artuso, E.; Barbero, M.; Degani, I.; Dughera, S.; Fochi, R. Tetrahedron 2006, 62,
3146e3157.
4.3.8. Diethyl
(E)-2-(4methoxycarbonylphenyl)vinylphosphonate
(34).34 Colorless oil; dH (400 MHz, CDCl3, 25 ꢀC) 1.35 (t,
3JH,H¼7.2 Hz, 6H), 3.83 (s, 3H), 4.07e4.17 (m, 4H), 6.09 (dd,
33. Buckley, B. R.; Neary, S. P. Adv. Synth. Catal. 2009, 351, 71e77.
2JH,P¼18.0 Hz, JH,H¼17.6 Hz, 1H), 6.90 (d, JH,H¼8.8 Hz, 2H), 7.45
34. Brunner, H.; Le Cousturier de Courcy, N.; Genet, J. P. Synlett 2000, 201e204.
3
3
^
Please cite this article in press as: El Bakouri, O.; et al., Tetrahedron (2013), http://dx.doi.org/10.1016/j.tet.2013.09.010